Bottom Line:
Detection of virus in the air was also significantly associated with transmission.This study is the first to identify statistically significant indicators of infectiousness for FMDV at defined time periods during disease progression in a natural host species.Identifying factors associated with infectiousness will advance our understanding of transmission mechanisms and refine intra-herd and inter-herd disease transmission models.

ABSTRACTThe control of foot-and-mouth disease virus (FMDV) outbreaks in non-endemic countries relies on the rapid detection and removal of infected animals. In this paper we use the observed relationship between the onset of clinical signs and direct contact transmission of FMDV to identify predictors for the onset of clinical signs and identify possible approaches to preclinical screening in the field. Threshold levels for various virological and immunological variables were determined using Receiver Operating Characteristic (ROC) curve analysis and then tested using generalized linear mixed models to determine their ability to predict the onset of clinical signs. In addition, concordance statistics between qualitative real time PCR test results and virus isolation results were evaluated. For the majority of animals (71%), the onset of clinical signs occurred 3-4 days post infection. The onset of clinical signs was associated with high levels of virus in the blood, oropharyngeal fluid and nasal fluid. Virus is first detectable in the oropharyngeal fluid, but detection of virus in the blood and nasal fluid may also be good candidates for preclinical indicators. Detection of virus in the air was also significantly associated with transmission. This study is the first to identify statistically significant indicators of infectiousness for FMDV at defined time periods during disease progression in a natural host species. Identifying factors associated with infectiousness will advance our understanding of transmission mechanisms and refine intra-herd and inter-herd disease transmission models.

Figure 3: Virus isolation (VI) vs qRT-PCR. Nonparametric regression comparing the two methods of virus detection (virus isolation and qRT-PCR) in both the OPF (A) and Blood (B). qRT-PCR is shown in pink and virus isolation method is shown in blue. The predicted line and 95% confidence intervals were done using PROC LOESS (SAS version 9.3). Smoothing parameter was 1.0 for OPF both VI and qRT-PCR and Blood qRT-PCR smoothing parameter for Blood VI was 0.67.

Mentions:
The pattern of virus detection with time (days) was similar for both the qRT-PCR and the virus isolation (VI) methods (Figure 3). Interestingly, virus in the OPF was always detected or not on a given day by both methods (Cohen’s kappa measure of agreement 1.00 (95% CIs 1.00-1.00)). However, agreement for detection of virus in the blood was lower (Cohen’s kappa 0.77 (95% CIs 0.62-0.93)). In general, in the blood low levels of virus were detected early post infection using the VI method when there was no virus detected using the qRT-PCR method. This may represent cell-associated virus. Viral genomes were detected using the qRT-PCR method late in study period, after there was no longer any virus detected using the VI method.

Figure 3: Virus isolation (VI) vs qRT-PCR. Nonparametric regression comparing the two methods of virus detection (virus isolation and qRT-PCR) in both the OPF (A) and Blood (B). qRT-PCR is shown in pink and virus isolation method is shown in blue. The predicted line and 95% confidence intervals were done using PROC LOESS (SAS version 9.3). Smoothing parameter was 1.0 for OPF both VI and qRT-PCR and Blood qRT-PCR smoothing parameter for Blood VI was 0.67.

Mentions:
The pattern of virus detection with time (days) was similar for both the qRT-PCR and the virus isolation (VI) methods (Figure 3). Interestingly, virus in the OPF was always detected or not on a given day by both methods (Cohen’s kappa measure of agreement 1.00 (95% CIs 1.00-1.00)). However, agreement for detection of virus in the blood was lower (Cohen’s kappa 0.77 (95% CIs 0.62-0.93)). In general, in the blood low levels of virus were detected early post infection using the VI method when there was no virus detected using the qRT-PCR method. This may represent cell-associated virus. Viral genomes were detected using the qRT-PCR method late in study period, after there was no longer any virus detected using the VI method.

Bottom Line:
Detection of virus in the air was also significantly associated with transmission.This study is the first to identify statistically significant indicators of infectiousness for FMDV at defined time periods during disease progression in a natural host species.Identifying factors associated with infectiousness will advance our understanding of transmission mechanisms and refine intra-herd and inter-herd disease transmission models.

ABSTRACTThe control of foot-and-mouth disease virus (FMDV) outbreaks in non-endemic countries relies on the rapid detection and removal of infected animals. In this paper we use the observed relationship between the onset of clinical signs and direct contact transmission of FMDV to identify predictors for the onset of clinical signs and identify possible approaches to preclinical screening in the field. Threshold levels for various virological and immunological variables were determined using Receiver Operating Characteristic (ROC) curve analysis and then tested using generalized linear mixed models to determine their ability to predict the onset of clinical signs. In addition, concordance statistics between qualitative real time PCR test results and virus isolation results were evaluated. For the majority of animals (71%), the onset of clinical signs occurred 3-4 days post infection. The onset of clinical signs was associated with high levels of virus in the blood, oropharyngeal fluid and nasal fluid. Virus is first detectable in the oropharyngeal fluid, but detection of virus in the blood and nasal fluid may also be good candidates for preclinical indicators. Detection of virus in the air was also significantly associated with transmission. This study is the first to identify statistically significant indicators of infectiousness for FMDV at defined time periods during disease progression in a natural host species. Identifying factors associated with infectiousness will advance our understanding of transmission mechanisms and refine intra-herd and inter-herd disease transmission models.